This proposal seeks to explore the factors underlying higher morbidity in minority groups with systemic lupus erythematosus by examining the relationship of socioeconomic, demographic, cultural, immunogenetic, and clinical variables to early outcome in a study of Hispanic, African- American, and Caucasian SLE patients from 2 geographic areas: Houston, Texas and Birmingham, Alabama. Since enrollment for the study began in April, 1994 and closed on January 10, 1996, a total of 229 patients meeting criteria for SLE have been enrolled, including 102 seen in the University Clinical Research Center at the University of Texas Health Science Center (63 Hispanics, 25 African- Americans and 14 Caucasians.) Immunogenetic analysis of these and the additional patients seen at The University of Alabama at Birmingham (n=112) and the University of Texas Medical Branch at Galveston (n=15) reveals an association with HLA-DRB1*0301 in Caucasians, DRB1*1503 in African -Americans and DRB1*08 in Hispanics. Preliminary analysis of the two year followup data in 160 of the 183 patients who have completed this visit indicate both genetic, sociodemographic and behavioral factors to independently predict cumulative disease damage as well as the persistence of disease activity over time. However, the persistence of ethnicity in the models as a predictive factor in disease damage and activity suggest that other (presumably non-MHC) genes are operative in affecting outcome in SLE. We have extended this study to include 62 additional patients from Mexico City, 28 from Cantabria, Spain, and 50 from Lima Peru, in order to examine the impacts of Native American versus Spanish Caucasian genes on the rate of accumulation of permanent damage due to SLE. Sociodemographic data have been collected and are currently under analysis. We were surprised to see the same HLA-DR8 association with SLE in the Peruvian mestizos that we saw in the Mexicans.